@article{3ac0d287f7f14596bc1dd0c9e0b6797a,
title = "Visualizing RNA conformational and architectural heterogeneity in solution",
abstract = "RNA flexibility is reflected in its heterogeneous conformation. Through direct visualization using atomic force microscopy (AFM) and the adenosylcobalamin riboswitch aptamer domain as an example, we show that a single RNA sequence folds into conformationally and architecturally heterogeneous structures under near-physiological solution conditions. Recapitulated 3D topological structures from AFM molecular surfaces reveal that all conformers share the same secondary structural elements. Only a population-weighted cohort, not any single conformer, including the crystal structure, can account for the ensemble behaviors observed by small-angle X-ray scattering (SAXS). All conformers except one are functionally active in terms of ligand binding. Our findings provide direct visual evidence that the sequence-structure relationship of RNA under physiologically relevant solution conditions is more complex than the one-to-one relationship for well-structured proteins. The direct visualization of conformational and architectural ensembles at the single-molecule level in solution may suggest new approaches to RNA structural analyses.",
author = "Jienyu Ding and Lee, {Yun Tzai} and Yuba Bhandari and Schwieters, {Charles D.} and Lixin Fan and Ping Yu and Tarosov, {Sergey G.} and Stagno, {Jason R.} and Buyong Ma and Ruth Nussinov and Alan Rein and Jinwei Zhang and Wang, {Yun Xing}",
note = "Funding Information: Open Access funding provided by the National Institutes of Health (NIH). Funding Information: This work was funded by the Intramural Research Program of the National Cancer Institute, National Institutes of Health (Y.-X.W.) and in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261201500003I (R.N.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. We thank Will F. Heinz for technical assistance in AFM, Benjamin Miller, Steve Fellini and Susan Chacko of the NIH HPC computing facility for allocating computing and storage resources for the project, and Dr. Jeffrey N. Strathern for his vision about RNA biology. Funding Information: This work was funded by the Intramural Research Program of the National Cancer Institute, National Institutes of Health (Y.-X.W.) and in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN261201500003I (R.N.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. We thank Will F. Heinz for technical assistance in AFM, Benjamin Miller, Steve Fellini and Susan Chacko of the NIH HPC computing facility for allocating computing and storage resources for the project, and Dr. Jeffrey N. Strathern for his vision about RNA biology. Publisher Copyright: {\textcopyright} 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.",
year = "2023",
month = dec,
doi = "10.1038/s41467-023-36184-x",
language = "English (US)",
volume = "14",
journal = "Nature communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}